5-aryl-3, 1, 4-benzoxadiazepine-2 (1h)-ones



United States Patent 3,152,145 5-ARYL-3,1

Newtown Square, 3 11., assignors to American Home Corporation, New York, NIL, a eorperation of Delawar Ne Drawing. Filed May 23, 1962, Ser. No. 1%,831

3 Claims. ill. 269-333) This invention relates to a new class of heterocyclic compounds having valuable pharmacologic effects. The new compounds of this invention may be named as S-aryl- 3,1,4-benzoxadiazepine-2(lH)-ones, and have the structure Where X is hydrogen, chlorine, bromine, methyl, or trifiuoromethyl, and Ar is an aromatic radical selected from the group consisting of phenyl, chlorophenyl, and nitrophenyl.

The new compounds of this invention potentiate the sedative efiects of barbiturates and also exhibit antiinfiammatory properties. Thus, administration of from 50 to 200 mg./l g. of the product of Example 1, below, greatly extends the duration of sleep induced by 50 rug/kg. of pentobarbital.

The compounds of this invention may be prepared by the interaction of phosgene and an appropriate Z-aminobenzophenone oxime in the presence of a tertiary base; the chemical reaction occurring may be abbreviated as follows:

OH 00012 X C=N \C=N tr it As is Well-known, the oXimes of unsymmetrical carbonyl compounds can exist in either of two stereoisomeric forms, usually designated as the synand antior cis and trans forms; for preparing compounds or" this invention, the form in which the oxime hydroxyl radical is cis with respect to the aminophenyl radical, is required.

The compounds of this invention may be combined or compounded with suitable diluents, solvents, carriers, fillers, etc., to produce dosage forms suitable for oral or parenteral administration.

The following examples illustrate the practice of this invention.

Example 1 A solution of 12 grams of Z-amino-S-chlorobenzophenone oXime (rt-form, hydroxyl cis with respect to substituted phenyl, MP. 170-173" C.), and 15 ml. of triethylamine in 150 ml. or" ethyl acetate is cooled in an ice bath. The solution is stirred vigorously while 40 grams of a 12.5% solution of phosgene in benzene is added dropwise, keeping the temperature below C.

fter addition is completed, the mixture is stirred for one-half hour at room temperature. The precipitated triethylamine hydrochloride is removed by filtration and the filtrate is concentrated in vacuo to a solid residue of 7-chloro-5-phenyl-3,1,4-benzoxadiazepine 2(1H)-one. The product may be recrystallized from ethyl acetate to yield colorless crystals. Dissolved in chloroform,

C6 3,152, 25 ented @et. 6, 1%54:

a La! the product exhibits UV. absorption maxima at 245 and 315 m it melts at C., the melt resolidifying and remelting at 312 C.

Analysis I C H N Cl Cal-2. for C nHgClNgO 3. 33 10. 27 13. 00 Found 3. 34 10. 23 12. 82

Example 2 By the procedure of Trample 1, using the syn oxime oi Z-amino-5-bromobenzophenone, ther is prepared '7-bromo-5-phenyl-3,1,4-benzoxadiazepine-2(1H)-0ne.

Example 3 By the procedure of Example 1, using the syn oxime of 2-amino-S-methylbenzophenone, there is prepared 7-methyl5-phenyl-3 ,1,4-benzoxadiazepine-2( 1H) -one.

Example 4 Example 6 By the procedure of Example 1, using the oxirne of Z-amino-5-chloro-4'-nitrobenzophenone in which the oxime hydroxyl is cis in respect to the amino-substituted phenyl group, there is produced 7-chloro-5-(p-nitrophenyl)-3,1,4-benzoXadiazepme-2(1H)-one.

We claim:

1. A 5-aryl-3,1,4-benzoxadiazepine-2(1H)-one having the formula C=N it where X is a member of the group consisting of hydrogen, chlorine, bromine, methyl and triiiuoromethyl and Ar is a member of the group consisting of phenyl, chlorophenyl and nitrophenyl.

2. 7-chloro-5-phenyl 3,1,4 benzoXad-iazepine2(1H)- one.

3. Process which comprises reacting phosgene and a Z-aminobenzophenone oxime having the formula where X is a member of the group consisting of hydrogen, chlorine, bromine, methyl and trifiuorornethyl, AI is a member of the group consisting of phenyl, chlorophenyl and nitrophenyl, and in Wm'ch the hydroxyl group is in the cis configuration with respect to the aminosubstituted phenyl radical in the presence of a tertiary amine base, and recovering a 5-aryl-3,1,4-benzoxadiazepine-2(1H)-one.

No references cited. 

1. A 5-ARYL-3,1,4-BENZOXADIAZEPINE-2(1H)-ONE HAVING THE FORMULA 